Chimeric antigen receptor (CAR) T cell therapy has led to a paradigm shift in cancer immunotherapy, but still several obstacles limit CAR T cell efficacy in cancers. Advances in high-throughput technologies revealed new insights into the role that epigenetic reprogramming plays in T cells. Mechanistic studies as well as comprehensive epigenome maps revealed an important role for epigenetic remodeling in T cell differentiation. These modifications shape the overall immune response through alterations in T cell phenotype and function. Here, we outline how epigenetic modifications in CAR T cells can overcome barriers limiting CAR T cell effectiveness, particularly in immunosuppressive tumor microenvironments. We also offer our perspective on how selected epigenetic modifications can boost CAR T cells to ultimately improve the efficacy of CAR T cell therapy.

嵌合抗原受体 (CAR) T 细胞疗法已导致癌症免疫疗法的范式转变，但仍有几个障碍限制了 CAR T 细胞在癌症中的功效。高通量技术的进步揭示了对表观遗传重编程在 T 细胞中的作用的新见解。机制研究以及全面的表观基因组图谱揭示了表观遗传重塑在 T 细胞分化中的重要作用。这些修饰通过改变 T 细胞表型和功能来塑造整体免疫反应。在这里，我们概述了 CAR T 细胞中的表观遗传修饰如何克服限制 CAR T 细胞有效性的障碍，特别是在免疫抑制性肿瘤微环境中。